Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) that infects and destroys helper Tlymphocytes. The general objective of this work is to devise strategies for introducing new genes into lymphocytes that will render them resistant to HIV infection. This approach has been described "intracellular immunization". We have first attempted antisense RNA inhibition of HIV replication. Although we have established a highly efficient retroviral mediated gene transfer system into CD4 T-cells an a sensitive assay system, the antisense strategy has proved ineffective in modifying HIV replication. We are currently examining several other possible antiviral gene products for this protocol. Rev and Gag are encoded by the HIV genome and are essential components for viral replication. It has been recently shown that mutants forms of these viral protein molecules interfere with HIV replication. The feasibility of using these mutant molecules in the intracellular immunization protocol will be tested in our assay system. We have established a stable cell line that express HIV envelope protein on cell surface at a very high level. This cell line will be very useful for studying the interaction between Env and CD4 molecules on cell surface and also can serve as a useful indicator for testing anti-HIV molecules targeting env, tat, and rev functions.